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991.
992.
Signalling by cGMP-dependent protein kinases 总被引:20,自引:0,他引:20
The second messenger cGMP is a major intracellular mediator of the vaso-active agents nitric oxide and natriuretic peptides. The principal targets of cGMP are (i) phosphodiesterases, resulting in interference with the CAMP-signalling pathway, (ii) cGMPgated cation channels, and (iii) cGMP-dependent protein kinases (cGKs). Only two mammalian isotypes of cGK have been described so far: type I cGK, consisting of an and a isoform, presumably splice variants of a single gene, and identified as the most prominent cGK isotype in the cardio-vascular system; and type II cGK, expressed mainly in the intestine, the kidney and the brain. High levels of cGK I are found in vascular smooth muscle cells, endothelial cells and platelets. In these cells, cGK I is thought to counteract the increase in contraction provoked by Ca-mobilizing agonists, to reduce endothelial permeability and to inhibit platelet aggregation, respectively. Relatively low levels of cGK I are found in cardiomyocytes. In this cell type, cGK is implicated in the negative inotropic effect of cGMP, presumably through modulation of Ca channels and by diminishing the Ca-sensitivity of contractile proteins. 相似文献
993.
The heat-stable enterotoxin STa of E. coli causes diarrhea by binding to and stimulating intestinal membrane-bound guanylyl cyclase, triggering production of cyclic GMP. Agents which stimulate protein kinase C (PKC), including phorbol esters, synergistically enhance STa effects on cGMP and secretion. We investigated whether PKC causes phosphorylation of the STa receptor in vivo and in vitro.Immunoprecipitation of the STa receptor-guanylyl cyclase was carried out from extracts of T84 colon cells metabolically labelled with [32P]-phosphate using polyclonal anti-STa receptor antibody. The STa receptor was phosphorylated in its basal state, and 32P content in the 150 kDa holoreceptor band increased 2-fold in cells exposed to phorbol ester for 1 h. In vitro, immunopurified STa receptor was readily phosphorylated by purified rat brain PKC. Phosphorylation was inhibited 40% by 5 M of a synthetic peptide corresponding to the sequence around Ser1029 of the STa receptor, a site previously proposed as a potential PKC phosphorylation site. Treatment of the immunopurified STaR/GC with purified PKC increased STa-stimulated guanylyl cyclase activity 2-fold. We conclude that PKC phosphorylates and activates the STa receptor/guanylyl cyclase in vitro and in vivo; Ser1029 of the STaR/GC remains a candidate phosphorylation site by PKC.Abbreviations STa
the heat-stable enterotoxin of E. coli, which has also been called ST-I and STp. The 18 amino acid variant was used throughout
- PBS
phosphate-buffered saline
- PDB
4--12, 13-phorbol dibutyrate
- ANP
atrial natriuretic peptide
- STaR/GC
STa receptor/guanylyl cyclase, also called GC-C
- PKC
protein kinase C 相似文献
994.
Shinichi Hatta Hiroki Ozawa Toshikazu Saito Hideyo Ohshika 《Journal of neurochemistry》1994,63(3):1104-1110
Abstract: The ability of the tubulin dimer to interact with and to modulate the Gi function inhibiting adenylyl cyclase was examined in cerebral cortex membranes from 2-month-old and 24-month-old rats. The hydrolysis-resistant GTP analogue 5'-guanylylimidodiphosphate (GppNHp)-dependent inhibition of adenylyl cyclase was significantly decreased in cerebral cortex membranes from 24-month-old rats. Tubulin, prepared from rat brains by polymerization with GppNHp, caused inhibition of adenylyl cyclase (∼28%) in 2-month-old rats. Tubulin-GppNHp-dependent inhibition of adenylyl cyclase in 24-month-old rats was significantly attenuated (∼15%). In 2-month-old rats, when tubulin, polymerized with the hydrolysis-resistant photoaffinity GTP analogue [32 P] P 3 (4-azidoanilido)- P 1 -5'-GTP ([32 P]AAGTP), was incubated with cerebral cortex membranes, AAGTP was transferred from tubulin to Giα . Transfer of AAGTP from tubulin to Giα was reduced in 24-month-old rats. Furthermore, photoaffinity labeling of [32 P]AAGTP to Giα in cortex membranes was significantly decreased in 24-month-old rats. No differences were observed in the amounts of Gsα , Giα , or Gβ subunits and tubulin, estimated by immunoblotting, in cortex membranes from 2-month-old and 24-month-old rats. These results suggest that the ability of tubulin to interact with Gi and thereby modulate the inhibitory regulation of adenylyl cyclase is reduced in the cerebral cortex of 24-month-old rats. 相似文献
995.
Randy Fenrick Kasimir Babinski Normand McNicoll Marc Therrien Jacques Drouin André De Léan 《Molecular and cellular biochemistry》1994,137(2):173-182
We describe the isolation of a 3,276 base pair cDNA for the bovine natriuretic peptide receptor-B (NPR-B). Expression of this clone in Cos-P cells demonstrates that it encodes an agonist-dependent guanylyl cyclase. Porcine CNP stimulates the activity of this receptor up to 200-fold with an ED50 of 12±2 nM, whereas brain natriuretic peptide C-type natriuretic peptide (CNP) and atrial natriuretic factor (ANF) are less efficacious. In addition, ligand binding studies indicate that this receptor exhibits the pharmacology appropriate for the bovine NPR-B. CNP binds to Cos-P cell membranes expressing this clone with a Kd of 13±1 pM, and natriuretic peptides compete for [125I]-CNP binding with a rank order of pCNP>pBNP>rANF. Thus, the expressed receptor-guanylyl cyclase exhibits the expected pharmacological profile for ligand binding and cyclase activation of the bovine NPR-B receptor.Abbreviations BSA
bovine serum albumin
- dNTP
deoxynucleotide triphosphate
- SDS
sodium dodecyl sulfate
- DEAE-dextran
diethylaminoethyl-dextran
- EDTA
ethylenediamine tetraacetic acid
- Tris
Tris(hydroxymethyl)aminomethane
- DMSO
dimethyl sulfoxide
- RP-HPLC
reverse phase-high performance liquid chromatography
- AMV
avian myeloblastosis virus
- Arg
arginine
- Lys
lysine 相似文献
996.
Catherine F. Welsh Joel Moss Martha Vaughan 《Molecular and cellular biochemistry》1994,138(1-2):157-166
ADP-ribosylation factors (ARFs) comprise a family of 20 kDa guanine nucleotide-binding proteins that were discovered as one of several cofactors required in cholera toxin-catalyzed ADP-ribosylation of Gs, the guanine nucleotide-binding protein responsible for stimulation of adenylyl cyclase, and was subsequently found to enhance all cholera toxin-catalyzed reactions and to directly interact with, and activate the toxin. ARF is dependent on GTP or its analogues for activity, binds GTP with high affinity in the presence of dimyristoylphosphatidylcholine/cholate and contains consensus sequences for GTP-binding and hydrolysis. Six mammalian family members have been identified which have been classified into three groups (Class I, II, and III) based on size, deduced amino acid sequence identity, phylogenetic analysis and gene structure. ARFs are ubiquitous among eukaryotes, with a deduced amino acid sequence that is highly conserved across diverse species. They have recently been shown to associate with phospholipid and Golgi membranes in a GTP-dependent manner and are involved in regulating vesicular transport.Abbreviations ARF
ADP-ribosylation factor
- sARF I and sARF II
soluble ADP-ribosylation factors purified from bovine brain
- mARF
purified membrane-associated ARF
- hARF
human ARF
- bARF
bovine ARF
- yARF
yeast ARF
- ARF
bacterially-expressed recombinant ARF
- gARF
Giardia ARF
- dARF
Drosophila ARF
- G protein
guanine nucleotide-binding protein
- Gs
G protein responsible for stimulation of adenylyl cyclase
- GTPS
guanosine-5-O-(3-thio-triphosphate)
- CIAI
cholera toxin A1 subunit
- DMPC
dimyristoylphosphatidylcholine
- SDS
sodium dodecyl sulfate 相似文献
997.
In the present work we used various cell lines in order to study the possible effect of coxsackievirus B3 (CVB3) entry on the adenylyl cyclase transmembrane signalling system. A significant decrease (by about 10–20%) was found in forskolin-augmented as well as in AlF
4
–
- and GTPS-sensitive adenylyl cyclase activity in plasma membranes isolated from HeLa, HEp-2, Vero and green monkey kidney cells shortly (up to 60 min) preincubated with CVB3 (5 PFU/cell). Moreover, the ability of G-proteins derived from plasma membranes of infected cells to reconstitute AC activity in the cyc– mutant of S49 cells was also reduced. Content of G-protein subunits, however, remained unchanged after CVB3 attachment. Functional alterations in the G-protein-mediated adenylyl cyclase signalling system were accompanied by a marked decrease (by about 20–40%) of intracellular cAMP levels in virus-affected cells. These findings demonstrate clearly that CVB3 may affect functioning of the G-protein regulated adenylyl cyclase transmembrane signalling system in virus-sensitive cells as early as during the first period of its contact with the cellular plasma membrane. 相似文献
998.
999.
《Free radical research》2013,47(3-6):265-274
Current dogma associates reperfusion injury with the introduction of reactive oxygen species (ROS) into the ischemic tissue. The sources of ROS under discussion are xanthine oxidase in the endothelium of small vessels and/or invaded polymorphonuclear leukocytes (PMN). The beneficial effects of both superoxide dismutase and catalase suggest an involvement of superoxide anions and hydrogen peroxide in this pathophysiological process, without describing the targets of their action.In our work we demonstrate that these two ROS effectively interact with two enzymes. Superoxide anions inhibit soluble guanylate cyclase. Its product, cGMP, is considedred to antagonize platelet activation and to cause smooth muscle relaxation. Thus O2 can intensify platelet aggregability and small vessel occlusion. Similar effects are elicited by H2O2, which shifts the dose response curve of several agonists towards smaller concentrations by activating cyclooxygenase. This enzyme provides the substrate for thromboxane synthase which generates TxA2, the most potent physiologically occurring platelet aggregating and smooth muscle contacting agonist.These results lead us to the suggestion that the influence of the oxidative burst of PMN in the phenomenon of reperfusion injury should be reconsidered. 相似文献
1000.